Real-world outcomes of Black versus non-Hispanic White women with stage IV HER2-low breast cancer treated with trastuzumab deruxtecan at an urban academic center.

Abstract

e13102 Background: Black women (BW) experience higher rates of advanced breast cancer and breast cancer mortality compared to Non-Hispanic White women (NHW). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved for HER2-positive, low, and ultra-low metastatic breast cancers. Black patients comprised < 5% of participants in the trials that led to T-DXd approval, leaving gaps in our understanding of response/toxicity in this population. To address this, we aimed to compare baseline characteristics, treatment outcomes, and toxicity profiles between BW and NHW with HER2-low metastatic breast cancer (mBC) treated with T-DXd at a racially diverse, tertiary care institution. Methods: BW and NHW patients with HER2-low mBC treated with T-DXd at Emory University between 2019 and 2024 were retrospectively evaluated. Descriptive statistics were generated for all patient characteristics. Univariate analyses and logistic regression models were used to assess clinical response, duration on therapy, dose modifications, and toxicity by race. Results: Eighty-two women with HER2-low mBC treated with T-DXd were included (BW n = 35 [43%], NHW n = 47 [57%]). Mean age at diagnosis and prior lines of therapy were similar between groups. BW had a higher prevalence of ER/PR-negative tumors compared with NHW (p < 0.006). Median duration of T-DXd therapy was comparable (147 days NHW vs 126 days BW; p = 0.73), as were treatment discontinuation rates (82% vs 89%; p = 0.74). Discontinuation due to progressive disease was numerically higher in BW (80% vs 63%, p = 0.19). Best response outcomes did not differ significantly: stable disease was most common (51.0% NHW vs 51.4% BW), while progressive disease occurred numerically more frequently in BW (40.0% vs 22.5%; p = 0.18). Interstitial lung disease, growth factor use, and non-hematologic toxicities including fatigue, nausea, and constipation were similar by race. There were low and comparable rates of grade 3–4 hematologic toxicities. BW had a trend toward worse overall survival compared with NHW (HR 1.89, 95% CI 0.93–3.83, p = 0.08). Conclusions: Our institutional data demonstrate no statistically significant differences in treatment response, discontinuation rates, or toxicities between NHW and BW with HER2-low mBC treated with T-DXd, although BW showed numerically higher rates of treatment discontinuation due to progressive disease and worse overall survival compared with NHW. Although these associations did not meet statistical significance, the direction suggest a potential survival disparity that may be underpowered in this cohort. The inclusion of diverse patients in clinical trials is essential to identify and address potential disparities in treatment responses and toxicities for all patients, particularly as we study novel agents in the frontline metastatic and early-stage settings.